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All 3 posts Subject: LSD and DOB: interaction with 5-HT2A receptors Please login to post Down

Rhodium
(Chief Bee)
04-24-02 19:24
No 300866
User Picture       LSD and DOB: interaction with 5-HT2A receptors
(Rated as: good read)

LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex
by
Arvanov VL, Liang X, Russo A, Wang RY
Department of Psychiatry and Behavioral Science,
SUNY at Stony Brook,
NY 11794-8790, USA
Eur J Neurosci 1999 Sep; 11(9):3064-72

ABSTRACT
Both the phenethylamine hallucinogen (-)-1-2, 5-dimethoxy-4-bromophenyl-2-aminopropane (DOB), a selective serotonin 5-HT2A,2C receptor agonist, and the indoleamine hallucinogen D-lysergic acid diethylamide (LSD, which binds to 5-HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D1 and D2, and alpha1 and alpha2 adrenergic receptors), but not their non-hallucinogenic congeners, inhibited N-methyl-D-aspartate (NMDA)-induced inward current and NMDA receptor-mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5-HT in the presence of selective 5-HT1A and 5-HT3 receptor antagonists. The inhibitory action of DOB, LSD and 5-HT on the NMDA transmission was blocked by the 5-HT2A receptor antagonists R-(+)-alpha-(2, 3-dimethoxyphenil)-1-[4-fluorophenylethyl]-4-piperidineme thanol (M100907) and ketanserin. However, at low concentrations, when both LSD and DOB by themselves only partially depressed the NMDA response, they blocked the inhibitory effect of 5-HT, suggesting a partial agonist action. Whereas N-(4-aminobutyl)-5-chloro-2-naphthalenesulphonamide (W-7, a calmodulin antagonist) and N-[2-[[[3-(4'-chlorophenyl)- 2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4'-methoxy-b enzenesulphonamide phosphate (KN-93, a Ca2+/CaM-KII inhibitor), but not the negative control 2-[N-4'methoxybenzenesulphonyl]amino-N-(4'-chlorophenyl)-2-propeny l-N -methylbenzylamine phosphate (KN-92), blocked the inhibitory action of LSD and DOB, the selective protein kinase C inhibitor chelerythrine was without any effect. We conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5-HT2A receptors via a Ca2+/CaM-KII-dependent signal transduction pathway as partial agonists and modulating the NMDA receptors-mediated sensory, perceptual, affective and cognitive processes.

Antoncho
(Official Hive Translator)
04-25-02 07:30
No 301160
      Interesting...

Makes one wonder if by chance there is any connection between the action of psychedelics and dissociatives (which, as we know, are noncompetitive NMDA antagonists).

Of course, NMDA receptor is so common in the brain that it's hard to associate any particular reaction with its blockade, but maybee thereis some specific network of such neurons that are responsible for "holding the reality intact" or "filtering out the unneeded stimuli" or, in Castanedian terms, "keeping the assemblage point in place" - that, when being gently inhibited (as we see in case of 5HT-2A-mediated action), 'soften' the reality's boundaries and, being rudely turned off by plugging up their NMDA channels (like in case of PCP), result in wild and chaotic experiences.

This is, of course, a very inscientific/far-fetched theory, but still rather cute, IMHO.

Antoncho

jsorex
(Hive Addict)
09-07-04 18:58
No 530146
      LSD and DOM increase extracellular glutamate
(Rated as: good read)

Well then look at this:

Lysergic acid diethylamide and -2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex
John W. Muschampa,1, Meredith J. Reginab,1, Elaine M. Hulla,b, Jerrold C. Winterb, Richard A. Rabin, Brain Research xx (2004)
DOI:10.1016/j.brainres.2004.07.044

Abstract

The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5- HT2A antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT2A/C agonist -2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 AM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.

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	All 3 posts		Subject: LSD and DOB: interaction with 5-HT2A receptors		Please login to post		Down


		Rhodium (Chief Bee) 04-24-02 19:24 No 300866				LSD and DOB: interaction with 5-HT2A receptors (Rated as: good read)
						LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex by Arvanov VL, Liang X, Russo A, Wang RY Department of Psychiatry and Behavioral Science, SUNY at Stony Brook, NY 11794-8790, USA Eur J Neurosci 1999 Sep; 11(9):3064-72 ABSTRACT Both the phenethylamine hallucinogen (-)-1-2, 5-dimethoxy-4-bromophenyl-2-aminopropane (DOB), a selective serotonin 5-HT2A,2C receptor agonist, and the indoleamine hallucinogen D-lysergic acid diethylamide (LSD, which binds to 5-HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D1 and D2, and alpha1 and alpha2 adrenergic receptors), but not their non-hallucinogenic congeners, inhibited N-methyl-D-aspartate (NMDA)-induced inward current and NMDA receptor-mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5-HT in the presence of selective 5-HT1A and 5-HT3 receptor antagonists. The inhibitory action of DOB, LSD and 5-HT on the NMDA transmission was blocked by the 5-HT2A receptor antagonists R-(+)-alpha-(2, 3-dimethoxyphenil)-1-[4-fluorophenylethyl]-4-piperidineme thanol (M100907) and ketanserin. However, at low concentrations, when both LSD and DOB by themselves only partially depressed the NMDA response, they blocked the inhibitory effect of 5-HT, suggesting a partial agonist action. Whereas N-(4-aminobutyl)-5-chloro-2-naphthalenesulphonamide (W-7, a calmodulin antagonist) and N-[2-[[[3-(4'-chlorophenyl)- 2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4'-methoxy-b enzenesulphonamide phosphate (KN-93, a Ca2+/CaM-KII inhibitor), but not the negative control 2-[N-4'methoxybenzenesulphonyl]amino-N-(4'-chlorophenyl)-2-propeny l-N -methylbenzylamine phosphate (KN-92), blocked the inhibitory action of LSD and DOB, the selective protein kinase C inhibitor chelerythrine was without any effect. We conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5-HT2A receptors via a Ca2+/CaM-KII-dependent signal transduction pathway as partial agonists and modulating the NMDA receptors-mediated sensory, perceptual, affective and cognitive processes.



		Antoncho (Official Hive Translator) 04-25-02 07:30 No 301160				Interesting...
						Makes one wonder if by chance there is any connection between the action of psychedelics and dissociatives (which, as we know, are noncompetitive NMDA antagonists). Of course, NMDA receptor is so common in the brain that it's hard to associate any particular reaction with its blockade, but maybee thereis some specific network of such neurons that are responsible for "holding the reality intact" or "filtering out the unneeded stimuli" or, in Castanedian terms, "keeping the assemblage point in place" - that, when being gently inhibited (as we see in case of 5HT-2A-mediated action), 'soften' the reality's boundaries and, being rudely turned off by plugging up their NMDA channels (like in case of PCP), result in wild and chaotic experiences. This is, of course, a very inscientific/far-fetched theory, but still rather cute, IMHO. Antoncho



		jsorex (Hive Addict) 09-07-04 18:58 No 530146				LSD and DOM increase extracellular glutamate (Rated as: good read)
						Well then look at this: Lysergic acid diethylamide and -2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex John W. Muschampa,1, Meredith J. Reginab,1, Elaine M. Hulla,b, Jerrold C. Winterb, Richard A. Rabin, Brain Research xx (2004) DOI:10.1016/j.brainres.2004.07.044 Abstract The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5- HT2A antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT2A/C agonist -2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 AM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.

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